Tetrabutylammonium Fluoride → (s)-Di-tert-butyl 4-(3-(2,3-difluorobenzyl)-1-methylureido)-5-hydroxypentyl phosphate

HRID 340976Notes

Reaction equation

HRID 340976 reaction equation
[P:1]([O:13][CH2:14][CH2:15][CH2:16][C@H:17]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=1[F:39])=[O:29])[CH2:18][O:19][Si](C(C)(C)C)(C)C)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[P:1]([O:13][CH2:14][CH2:15][CH2:16][C@H:17]([N:27]([CH3:40])[C:28]([NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=1[F:39])=[O:29])[CH2:18][OH:19])([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57947500(s)-Di-tert-butyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentyl phosphate

Product 1

HCID 57947552(s)-Di-tert-butyl 4-(3-(2,3-difluorobenzyl)-1-methylureido)-5-hydroxypentyl phosphateYield 64.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-di-tert-butyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentyl phosphate (4.1 g, 7.95 mmol) in THF (40 mL) was added TBAF (1.0 M in THF, 8.0 mL, 8.0 mmol). The resulting solution was stirred at RT for 1 h. The mixture was quenched with sat. NH4Cl and diluted with EtOAc. The organic layer was washed with sat. NH4Cl (×2) and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-di-tert-butyl 4-(3-(2,3-difluorobenzyl)-1-methylureido)-5-hydroxypentyl phosphate (2.52 g, 61%) as a colorless oil. LRMS (M+H+−2 tBu) m/z 383.0.

Workup

  1. customThe mixture was quenched with sat. NH4Cl
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with sat. NH4Cl (×2) and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified on silica gel column
  8. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-e45db784d7754c6cb8abd4a5dda09d61
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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